A Study of Enzastaurin in Participants With Follicular Lymphoma

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00475644
• Collaborator: (none)
• Enrollment: 66
• Locations: 23
• Arm: 1
• Duration (Months): 91
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To evaluate the antitumor activity, as measured by tumor response rate, of enzastaurin in participants with Follicular Lymphoma (FL).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Follicular	Drug: Enzastaurin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Enzastaurin in Participants With Follicular Lymphoma
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enzastaurin Enzastaurin: 1125 milligram (mg) loading dose then 500 mg, oral daily, up to 3 years	Drug: Enzastaurin; Administered orally; Other Names: LY317615

Outcome Measures

Primary Outcome Measures

1. Tumor Response Rate (RR) (Percentage of Participants Exhibiting Complete Response [CR] or Complete Response Unconfirmed [CRu] or Partial Response [PR]) [Baseline to Measured Progressive Disease (up to 1559 Days)]

   Tumor response rate is defined as the number of responders divided by the number of treated patients. A responder is a patient who exhibits a complete response (CR), complete response unconfirmed (CRu), or partial response (PR) as defined by Cheson et al. CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [Baseline to Measured Progressive Disease or Death from Any Cause (Up to 1559 Days)]

   PFS is defined as the time from the date of study enrollment to the first date of measured progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy. For reference, PFS will also be calculated and analyzed based on an alternative definition of censoring: for each patient who is not known to have died or to have had objective progression of disease as of the data cut-off date, PFS will be censored for that analysis at the date of last prior contact.

2. Time to Response (TtR) [Baseline to Date of Confirmed Response (Up to 890 Days)]

   TtR is defined as the time from the date of study enrollment to the date of response (CR, CRu, or PR) for patients who have responded prior to receiving any subsequent anticancer therapy.CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.

3. Duration of Response (DoR) [Time of Response to Measured Progressive Disease (Up to 1415 Days)]

   DoR is defined as the time from the date when the measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the date of first observation of measured progressive disease. For responding participants who die without progressive disease (including death from study disease), DoR will be censored at the date of death. For responding participants not known to have died as of the data cut-off date and who do not have progressive disease, DoR will be censored at the last objective progression-free assessment date prior to the data cut-off date. For responding participants who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression, DoR will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy.

4. Number of Participants With Response With Expression of Protein Biomarkers [Baseline]

   Correlative analyses of tumor RR for PKC-β2 (protein kinase C-β) protein expression. Immunohistochemistry (IHC) staining was performed to assess protein expression of PKC-β2 in cytoplasm reported as H scores (logistic model of response rate), which was derived from a weighted average of staining intensity (scale 0 to 3, increasing intensity) and percentage of positive cells (0 to 100%) at each staining intensity. PKC-β2 expression was further classified into high vs. low expression using the cutpoint of the median of the distribution of PKC-β2 H scores.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

All participants must:

1. Have had a histologically confirmed diagnosis of Grade 1 or 2 FL, according to World Health Organization classification (Harris et al. 1999), at the original time of diagnosis. Pathology must be confirmed locally prior to enrollment at the investigational site.

2. Have Ann Arbor Stage III or IV disease.

3. Must be chemo-naive OR have relapsed disease after receiving only one prior chemotherapy regimen. The chemotherapy must have been completed at least 6 months prior to first dose of study treatment. Relapse after one prior course of single-agent rituximab treatment (in the chemo-naive setting) is also allowed if completed at least 6 months prior to first dose of study treatment.

4. Participants must not require cytoreductive therapy for at least 3 months from first dose of study treatment, in the opinion of the investigator.

5. Previous radiation therapy is allowed, but should have been limited and must not have included whole pelvis radiation. Participants must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study entry. Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.

Exclusion Criteria:

Participants will be excluded from the study if they meet any of the following criteria:

1. Are unable to swallow tablets.

2. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin.

3. Are receiving concurrent administration of any other antitumor therapy.

4. Are pregnant or breastfeeding.

5. Have a serious concomitant systemic disorder (including active bacterial, fungal, or viral infection) that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Casa Grande	Arizona	United States	85222
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	La Verne	California	United States	91750
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Los Angeles	California	United States	90027
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sacramento	California	United States	95816
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Myers	Florida	United States	33916
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Augusta	Georgia	United States	30901
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Marietta	Georgia	United States	30060
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Coeur d'Alene	Idaho	United States	83814
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lafayette	Indiana	United States	47904
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Billings	Montana	United States	59101
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cincinnati	Ohio	United States	45242
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lawton	Oklahoma	United States	73505
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Philadelphia	Pennsylvania	United States	19107
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chattanooga	Tennessee	United States	37404
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Memphis	Tennessee	United States	38120
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nashville	Tennessee	United States	37203
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Richmond	Virginia	United States	23230
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	La Crosse	Wisconsin	United States	54601
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	D-12203
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bielefeld		Germany	D-33604
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	D 21075
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kiel		Germany	24040
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Munich		Germany	81377

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours,EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00475644
• Other Study ID Numbers: 8671; H6Q-MC-S011
• First Posted: May 21, 2007
• Last Update Posted: Nov 5, 2018
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular

Study Results

Participant Flow

Pre-assignment Detail	Participants who were considered to have completed the study who received at least 1 dose of study drug, did not have any protocol violations, and from whom a valid assay result was obtained.

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
Period Title: Overall Study
STARTED	66
Received at Least One Dose of Study Drug	66
COMPLETED	53
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
Overall Participants	66
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.55 (11.851)
Sex: Female, Male (Count of Participants)
Female	43 65.2%
Male	23 34.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.5%
Not Hispanic or Latino	63 95.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 3%
White	61 92.4%
More than one race	0 0%
Unknown or Not Reported	3 4.5%

Outcome Measures

1. Primary Outcome

Title	Tumor Response Rate (RR) (Percentage of Participants Exhibiting Complete Response [CR] or Complete Response Unconfirmed [CRu] or Partial Response [PR])
Description	Tumor response rate is defined as the number of responders divided by the number of treated patients. A responder is a patient who exhibits a complete response (CR), complete response unconfirmed (CRu), or partial response (PR) as defined by Cheson et al. CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.
Time Frame	Baseline to Measured Progressive Disease (up to 1559 Days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug and did not violate any study criteria.

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
Measure Participants	53
Number (95% Confidence Interval) [percentage of participants]	26.4 40%

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS is defined as the time from the date of study enrollment to the first date of measured progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy. For reference, PFS will also be calculated and analyzed based on an alternative definition of censoring: for each patient who is not known to have died or to have had objective progression of disease as of the data cut-off date, PFS will be censored for that analysis at the date of last prior contact.
Time Frame	Baseline to Measured Progressive Disease or Death from Any Cause (Up to 1559 Days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug and who did not violate any study entry criteria. There were 18 censored participants.

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
Measure Participants	53
Median (95% Confidence Interval) [Days]	551.0

3. Secondary Outcome

Title	Time to Response (TtR)
Description	TtR is defined as the time from the date of study enrollment to the date of response (CR, CRu, or PR) for patients who have responded prior to receiving any subsequent anticancer therapy.CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.
Time Frame	Baseline to Date of Confirmed Response (Up to 890 Days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug and did not violate any study entry criteria and who had baseline and post-baseline response data.

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
Measure Participants	14
Median (95% Confidence Interval) [Days]	148.0

4. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR is defined as the time from the date when the measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the date of first observation of measured progressive disease. For responding participants who die without progressive disease (including death from study disease), DoR will be censored at the date of death. For responding participants not known to have died as of the data cut-off date and who do not have progressive disease, DoR will be censored at the last objective progression-free assessment date prior to the data cut-off date. For responding participants who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression, DoR will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy.
Time Frame	Time of Response to Measured Progressive Disease (Up to 1415 Days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug, did not violate any study entry criteria and had baseline and post-baseline response data. There were 4 censored participants.

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
Measure Participants	14
Median (95% Confidence Interval) [Days]	677.5

5. Secondary Outcome

Title	Number of Participants With Response With Expression of Protein Biomarkers
Description	Correlative analyses of tumor RR for PKC-β2 (protein kinase C-β) protein expression. Immunohistochemistry (IHC) staining was performed to assess protein expression of PKC-β2 in cytoplasm reported as H scores (logistic model of response rate), which was derived from a weighted average of staining intensity (scale 0 to 3, increasing intensity) and percentage of positive cells (0 to 100%) at each staining intensity. PKC-β2 expression was further classified into high vs. low expression using the cutpoint of the median of the distribution of PKC-β2 H scores.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The TR (Translational Research) population consisted of participants from whom tumor tissue was obtained.

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
Measure Participants	12
High Expression	1 1.5%
Low Expression	5 7.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.031
	Confidence Interval	(2-Sided) 95%; 0.001 to 0.860
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Enzastaurin
Arm/Group Description	Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
All Cause Mortality
	Enzastaurin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Enzastaurin
	Affected / at Risk (%)	# Events
Total	16/66 (24.2%)
Cardiac disorders
Angina pectoris	1/66 (1.5%)	1
Palpitations	1/66 (1.5%)	1
Eye disorders
Visual acuity reduced	1/66 (1.5%)	1
Gastrointestinal disorders
Diarrhoea	1/66 (1.5%)	2
Gastrooesophageal reflux disease	1/66 (1.5%)	1
Pancreatitis	1/66 (1.5%)	1
Pancreatitis acute	1/66 (1.5%)	1
Hepatobiliary disorders
Cholecystitis	1/66 (1.5%)	1
Cholelithiasis	1/66 (1.5%)	2
Infections and infestations
Bronchitis	1/66 (1.5%)	1
Sepsis	1/66 (1.5%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/66 (1.5%)	6
Femur fracture	1/66 (1.5%)	1
Fractured sacrum	1/66 (1.5%)	2
Incisional hernia	1/66 (1.5%)	1
Metabolism and nutrition disorders
Dehydration	1/66 (1.5%)	1
Failure to thrive	1/66 (1.5%)	1
Hypertriglyceridaemia	1/66 (1.5%)	1
Hypokalaemia	1/66 (1.5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/66 (1.5%)	2
Prostate cancer	1/23 (4.3%)	3
Rectal adenoma	1/66 (1.5%)	1
Psychiatric disorders
Mental status changes	1/66 (1.5%)	1
Renal and urinary disorders
Renal mass	1/66 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/66 (1.5%)	1
Pulmonary embolism	1/66 (1.5%)	1
Vascular disorders
Deep vein thrombosis	1/66 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Enzastaurin
	Affected / at Risk (%)	# Events
Total	58/66 (87.9%)
Blood and lymphatic system disorders
Anaemia	9/66 (13.6%)	36
Cardiac disorders
Palpitations	4/66 (6.1%)	19
Gastrointestinal disorders
Abdominal distension	7/66 (10.6%)	29
Abdominal pain	8/66 (12.1%)	22
Abdominal pain upper	5/66 (7.6%)	22
Constipation	10/66 (15.2%)	53
Diarrhoea	20/66 (30.3%)	121
Dyspepsia	6/66 (9.1%)	38
Faeces discoloured	10/66 (15.2%)	91
Flatulence	5/66 (7.6%)	21
Nausea	19/66 (28.8%)	77
Stomatitis	5/66 (7.6%)	12
Vomiting	5/66 (7.6%)	5
General disorders
Fatigue	25/66 (37.9%)	139
Oedema peripheral	6/66 (9.1%)	26
Infections and infestations
Nasopharyngitis	4/66 (6.1%)	12
Oral herpes	4/66 (6.1%)	13
Rhinitis	4/66 (6.1%)	5
Sinusitis	5/66 (7.6%)	11
Upper respiratory tract infection	5/66 (7.6%)	10
Urinary tract infection	5/66 (7.6%)	6
Metabolism and nutrition disorders
Decreased appetite	4/66 (6.1%)	10
Musculoskeletal and connective tissue disorders
Arthralgia	11/66 (16.7%)	56
Back pain	9/66 (13.6%)	44
Musculoskeletal pain	4/66 (6.1%)	22
Nervous system disorders
Dizziness	8/66 (12.1%)	50
Headache	11/66 (16.7%)	69
Psychiatric disorders
Insomnia	5/66 (7.6%)	34
Renal and urinary disorders
Chromaturia	14/66 (21.2%)	114
Respiratory, thoracic and mediastinal disorders
Cough	13/66 (19.7%)	36
Dyspnoea	8/66 (12.1%)	43
Oropharyngeal pain	4/66 (6.1%)	6
Skin and subcutaneous tissue disorders
Dry skin	4/66 (6.1%)	26
Hyperhidrosis	4/66 (6.1%)	21
Night sweats	8/66 (12.1%)	36
Rash	6/66 (9.1%)	27
Rash pruritic	4/66 (6.1%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.